What can cause Vitamin D deficiency?

1.

Koppel, Barbara S., Weimer, Louis H., Daras, Michael (2024). In Goldman-Cecil Medicine (pp. 2537). DOI: 10.1016/B978-0-323-93038-3.00384-1

Vitamin D deficiency is often diagnosed in asymptomatic adults because of frequent screening, despite the U.S. Preventive Services Task Force’s recommendations against screening (Chapter 199).Although there is no absolutecutoff, serum levels of 25(OH) D below 30 nmol/L can cause parathyroid dysfunction with subsequent dysregulation of calcium and serum electrolytes (Chapter 227). Deficiency results from impaired skin synthesis owing to inadequate exposure to sunlight, dietary insufficiency, intestinal malabsorption; or sequestration of the vitamin as it is stored in fat cells of obese patients. The average multivitamin contains 400 IU of combined D2(ergocalciferol) and D3(cholecalciferol), whereas 20minutes of full-body summer sun exposure provides 10,000 IU of D3, the form used in the body.

2.

Greenbaum, Larry A. (2025). Vitamin D Deficiency (Rickets) and Excess. In Nelson Textbook of Pediatrics (pp. 470). DOI: 10.1016/B978-0-323-88305-4.00069-9

Along with inadequate intake, vitamin D deficiency can result from inadequate absorption, decreased hydroxylation in the liver, and increased degradation. Because vitamin D is fat soluble, its absorption may be decreased in patients with a variety of liver and GI diseases, including cholestatic liver disease, defects in bile acid metabolism, cystic fibrosis and other causes of pancreatic dysfunction, celiac disease, and Crohn disease. Malabsorption of vitamin D can also occur with intestinal lymphangiectasia and after intestinal resection. Severe liver disease, which usually is also associated with malabsorption, can cause a decrease in 25-D formation as a result of insufficient enzyme activity. Because of the large reserve of 25-hydroxlase activity in the liver, vitamin D deficiency caused by liver disease usually requires a loss of >90% of liver function. A variety of medications increase the degradation of vitamin D by inducing the cytochrome P450 (CYP) system. Rickets from vitamin D deficiency can develop in children receiving anticonvulsants (e.g., phenobarbital, phenytoin) or antituberculosis medications (e.g., isoniazid, rifampin).

3.

Elsevier ClinicalKey Clinical Overview

Diagnosis Insufficient dietary vitamin D (cholecalciferol [D₃] or ergocalciferol [D₂]) Malnutrition Inadequate cutaneous production of cholecalciferol Seasonal or permanent residence in far northern or southern latitudes Patients who are institutionalized or homebound Limited sun exposure due to protective clothing Sunscreen use Increased skin pigmentation Inability to process vitamin D due to renal or liver failure Conversion of vitamins D₂ and D₃ into active compounds requires a 2-step enzymatic hydroxylation process First step occurs with 25-hydroxylase activity in the liver, and second step occurs with 1α-hydroxylase activity in the kidney Level of hepatic and renal dysfunction required for this enzymatic dysfunction is significant (cirrhosis and renal failure, respectively) Intestinal malabsorption of vitamin D due to: Exocrine pancreatic insufficiency Inflammatory bowel disease Sarcoidosis Amyloidosis Celiac disease Cystic fibrosis Bariatric surgery Small intestine resection/short bowel syndrome Drug-induced impairment of vitamin D action or drug-provoked vitamin D catabolism due to: Phenobarbital Phenytoin Rifampin Antiretroviral therapy Glucocorticoids 1α-hydroxylase deficiency

4.

Elsevier ClinicalKey Clinical Overview

Diagnosis Deficient dietary intake of cholecalciferol (D₃)/ergocalciferol(D₂) or deficient cutaneous synthesis of cholecalciferol (represents approximately 95% of cases Malnutrition Simple inadequate intake as a result of exclusive breastfeeding or insufficient consumption of vitamin D–fortified dairy products Deficient cutaneous synthesis of 25-hydroxyvitamin D is caused by inadequate sunlight (UV-B) exposure Conditions affecting intestinal absorption approximately 5% of cases Whipple disease Cystic fibrosis Celiac disease Parenchymal or cholestatic liver disease Inflammatory bowel disease Drugs that affect the absorption, metabolism, or activation of vitamin D ( less than 1% of cases Glucocorticoids Rifampin Highly active antiretroviral therapy Antiepileptic drugs

Diagnosis Subsubsection Title: Genetics: Hereditary vitamin D–dependent rickets (rare inherited disorders) Vitamin D–dependent rickets type 1A (OMIM #264700) CYP27B1 gene, coding for 25-hydroxyvitamin D₃–1α-hydroxylase Vitamin D–dependent rickets type 1B (OMIM #600081) CYP2R1 gene, coding for 25-hydroxylase Vitamin D–dependent rickets type 2 (OMIM #277440) VDR gene, coding for the vitamin D receptor Subsubsection Title: Ethnicity/race: Ethnicities with dark pigmentation (non-White) are at higher risk Melanin absorbs UV-B radiation and reduces vitamin D₃ synthesis Require longer sun exposure than people with white skin to synthesize the same amount of vitamin D₃ Subsubsection Title: Other risk factors/associations: Factors reducing exposure of skin to solar UV-B Overzealous use of sunscreen with sun protection factor 30 or higher: reduces biosynthesis of vitamin D₃ by more than 95% Living in high-latitude areas (latitude higher than 40° north or south) Cultural practices that encourage covering most or all skin Prolonged and exclusive breastfeeding Breast milk is a poor source of vitamin D, and the amount contained is insufficient on its own to prevent deficiency in an infant unless the mother is taking high doses (4000 international units daily) of vitamin D supplements Infants breastfed from vitamin D–replete mothers will have vitamin D levels below reference range after 8 weeks of exclusive breastfeeding Eating disorders (eg, bulimia nervosa, anorexia nervosa) Picky eating in which children exclude milk and milk products, eggs, and other dietary sources of vitamin D Lactose intolerance causing avoidance of milk

5.

Mousavi SE, Amini H, Heydarpour P, Amini Chermahini F, Godderis L. Environment International. 2019;122:67-90. doi:10.1016/j.envint.2018.11.052.

Publish date: January 2, 2019.

Heavy metals may reduce VD serum levels by increasing renal tubular dysfunction, as well as downregulating the transcription of cytochrome P450 mixed-function oxidases (CYPs). Endocrine-disrupting chemicals (EDCs) may inhibit the activity and expression of CYPs, and indirectly cause VDD through weight gain and dysregulation of thyroid hormone, parathyroid hormone, and calcium homeostasis. Smoking through several pathways decreases serum 25(OH)D and 1,25(OH)2D levels, VD intake from diet, and the cutaneous production of VD through skin aging. In summary, disturbance in the cutaneous production of cholecalciferol, decreased intestinal intake of VD, the modulation of genes involved in VD homeostasis, and decreased local production of calcitriol in target tissues are the most likely mechanisms that involve in decreasing the serum VD levels.